Qian Bei-Bei, Huang Yu-Jie, Yan Cai-Feng, Feng Shang-Yong, She Dun-Min
Northern Jiangsu People's Hospital Northern Jiangsu People's Hospital Affiliated to Yangzhou University Yangzhou Jiangsu China.
Huaian Cancer Hospital Huaian Jiangsu China.
Obes Sci Pract. 2025 Aug 22;11(4):e70090. doi: 10.1002/osp4.70090. eCollection 2025 Aug.
Glucagon-like peptide-1 receptor (GLP-1R) agonists are well-established therapies for obesity and type 2 diabetes mellitus (T2DM). Emerging evidence also suggests their potential role in managing obstructive sleep apnea (OSA). This study aimed to investigate the association between GLP-1R agonists and OSA using genetic evidence.
Cis-expression quantitative trait loci (cis-eQTLs) associated with the gene were identified and used as genetic proxies for GLP-1R agonist exposure. To validate the selected genetic instruments, positive control analyses were conducted for T2DM and body mass index (BMI). Mendelian randomization was employed to evaluate the effect of genetically proxied GLP-1R agonists on OSA. OSA data were obtained from FinnGen Release 11 (R11), comprising 50,200 cases and 401,484 controls of European ancestry. The inverse variance weighted (IVW) method served as the primary analytical approach, supplemented by heterogeneity tests and sensitivity analyses.
IVW analysis showed that genetically predicted GLP-1R agonist exposure was associated with a reduction in BMI ( = -0.063, 95% confidence interval [CI]: -0.10 to -0.03, = 8.43 × 10) and a decreased risk of T2DM (odds ratio [OR] = 0.80, 95% CI: 0.65 to 0.98, = 0.032), supporting the validity of the genetic instruments. Notably, GLP-1R agonists were also associated with a significantly lower risk of OSA (OR = 0.83, 95% CI: 0.76 to 0.91, = 6.15 × 10). No evidence of heterogeneity or horizontal pleiotropy was detected, and leave-one-out analysis confirmed the robustness of the findings.
This study provides genetic evidence supporting the protective role of GLP-1R agonists against OSA, highlighting their potential as a therapeutic strategy for OSA management.
胰高血糖素样肽-1受体（GLP-1R）激动剂是治疗肥胖症和2型糖尿病（T2DM）的成熟疗法。新出现的证据还表明它们在治疗阻塞性睡眠呼吸暂停（OSA）中可能发挥的作用。本研究旨在利用遗传证据探讨GLP-1R激动剂与OSA之间的关联。
鉴定与该基因相关的顺式表达定量性状位点（cis-eQTLs），并将其用作GLP-1R激动剂暴露的遗传代理。为了验证所选的遗传工具，对T2DM和体重指数（BMI）进行了阳性对照分析。采用孟德尔随机化方法评估遗传代理的GLP-1R激动剂对OSA的影响。OSA数据来自芬兰基因库发布的第11版（R11），包括50200例病例和401484例欧洲血统对照。逆方差加权（IVW）方法作为主要分析方法，并辅以异质性检验和敏感性分析。
IVW分析表明，遗传预测的GLP-1R激动剂暴露与BMI降低（β = -0.063，95%置信区间[CI]：-0.10至-0.03，P = 8.43×10⁻⁴）以及T2DM风险降低（比值比[OR] = 0.80，95% CI：0.65至0.98，P = 0.032）相关，支持了遗传工具的有效性。值得注意的是，GLP-1R激动剂还与OSA风险显著降低相关（OR = 0.83，95% CI：0.76至0.91，P = 6.15×10⁻⁶）。未检测到异质性或水平多效性的证据，留一法分析证实了研究结果的稳健性。
本研究提供了遗传证据，支持GLP-1R激动剂对OSA的保护作用，突出了它们作为OSA治疗策略的潜力。
